CD20 is a transmembrane protein that is expressed on more than 95% of B-lymphocytes. Expression at the cell surface occurs from the pre-B stage of development until differentiation to a plasma cell. In human medicine, an anti-CD20 monoclonal antibody therapeutic (e.g., Rituximab) has been used to treat relapsed or refractory non-Hodgkin's lymphoma (NHL), as a first-line therapy for NHL as well as diffuse large B-cell lymphoma, and as an adjunct therapy for NHL. Although expression of CD20 has been shown to correlate with B-cell lymphoma in the dog (Jubala et al., Vet. Path., (2005) 42:468-76), the human therapeutic is not able to bind or deplete canine B-cells ex vivo (Impellizeri et al., Vet. J. (2006) 171:556-8). Therefore, compositions and methods of treatment of B-cell lymphoma, rheumatoid arthritis, immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, systemic lupus erythematosus, autoimmune disease, or other diseases that are characterized by the presence of too many B cells, overactive or over-expressed B cells or dysfunctional B cells are needed in the dog.